Determination of the 50% Human Infectious Dose for Norwalk Virus

Determination of the 50% Human Infectious Dose for Norwalk Virus
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DOI:
10.1093/infdis/jit620
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发表时间:
2014-04-01
影响因子:
6.4
通讯作者:
Graham, David Y.
Graham, David Y.
中科院分区:
医学2区
文献类型:
--
作者:
Atmar, Robert L.;Opekun, Antone R.;Graham, David Y.

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背景资料。诺如病毒是美国胃肠炎的最常见原因。了解这些病毒的感染剂量对于风险评估研究很重要。健康成年人参加了对不同剂量诺沃克病毒的随机、双盲、安慰剂对照评估。对符合条件的受试者进行临床胃肠炎监测,并确定感染状况。同时还检测了呕吐物中病毒的存在。57人参加了试验;8人接受了安慰剂治疗,另外8人因分泌物阴性而被认为不受影响。21人被感染(都是O型或A型),67%的感染者发展为病毒性胃肠炎。对于分泌型血型O或A血型阳性的人,50%的人类感染剂量计算为3.3逆转录聚合酶链式反应单位(约1320基因组当量[gEq]),对于所有分泌型阳性者为7.0(约2800 gEq)。发病时间与接种量呈负相关。胃肠炎患者排出病毒的最大浓度较高。27份呕吐物中有15份(56%)检出诺沃克病毒,病毒中位数为41000 gEq/ml。测得的人类感染剂量的50%高于先前的估计,与其他RNA病毒的剂量相似。
Background. Noroviruses are the most common cause of gastroenteritis in the United States. An understanding of the infectious dose of these viruses is important for risk assessment studies.Methods. Healthy adults were enrolled in a randomized, double-blind, placebo-controlled evaluation of different dosages of Norwalk virus. Eligible subjects were monitored for clinical gastroenteritis, and infection status was determined. The presence of virus in vomitus was also assessed.Results. Fifty-seven persons were enrolled; 8 received placebo and an additional 8 persons were considered to be nonsusceptible on the basis of being secretor negative. Twenty-one persons were infected (all blood group O or A), and 67% of those infected developed viral gastroenteritis. The 50% human infectious dose was calculated to be 3.3 reverse transcription polymerase chain reaction units (approximately 1320 genomic equivalents [gEq]) for secretor-positive blood group O or A persons and 7.0 (approximately 2800 gEq) for all secretor-positive persons. The time of illness onset was inversely correlated with inoculum dose. The maximal concentration of virus shedding was higher for persons with gastroenteritis. Norwalk virus was identified in 15 of 27 (56%) vomitus samples at a median concentration of 41 000 gEq/mL.Conclusions. The 50% human infectious dose measured is higher than previous estimates and similar to that of other RNA viruses.